title: Valsartan, an angiotensin II receptor blocker, attenuates cardiac dysfunction and oxidative stress in isoproterenol-induced cardiotoxicity.
abstract: Valsartan has significant blood pressure lowering effect via modulating renin-angiotensin system although its mechanism of action in isoproterenol (ISO)-induced myocardial injury is largely unknown. We therefore evaluated the effect of valsartan in ISO-induced oxidative stress and cardiotoxicity during β-adrenergic receptor stimulation in rats. ISO (85 mg/kg, s.c.) was administered on thirteenth and fourteenth day for induction of cardiotoxicity. ISO-treated rats showed significant decrease (P < 0.01) in mean arterial pressure (70.2 ± 9.11 vs. 104.86 ± 8.93), maximal positive (1601.3 ± 338.87 vs. 2789.16 ± 301.76), and negative (1495.76 ± 151.78 vs. 2039.6 ± 279.1) rate of developed left ventricular pressure and increase in left ventricular end-diastolic pressure (5.81 ± 0.51 vs. 2.37 ± 0.43) as compared to the sham group. Similarly, significant reduction in CK-MB (91.42 ± 5.88 vs. 142.63 ± 6.9), LDH (50.52 ± 5.18 vs. 73.28 ± 4.29) levels, and anti-oxidant enzymes activities were observed. Valsartan (15, 30, and 60 mg/kg/day, p.o.) pretreatment for 14 days favorably modulated these altered parameters. However, valsartan (60 mg/kg) only showed significant improvement (P < 0.01) in cardiac dysfunction, myocardial injury markers, and anti-oxidant status of myocardium in ISO-induced cardiotoxicity. Histopathology and ultrastructural studies further validated the protective effect of valsartan (60 mg/kg). Altogether, these results suggest that cardioprotective effect of valsartan is mediated through augmenting endogenous anti-oxidant defense system, preserving hemodynamic function and structural integrity of myocardium.
authors.affiliation: Cardiovascular Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Sameer
authors.initials: S
authors.lastname: Goyal
authors.forename: Saurabh
authors.initials: S
authors.lastname: Bharti
authors.forename: Kanhei Charan
authors.initials: KC
authors.lastname: Sahoo
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Sharma
authors.forename: Dharamvir Singh
authors.initials: DS
authors.lastname: Arya
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D054715:Cardiotoxins / Q000633:toxicity; D006331:Heart Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol / Q000633:toxicity*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D002316:Cardiotonic Agents; D054715:Cardiotoxins; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; D007545:Isoproterenol